The disclosure pertains to methods and devices for delivering material to individual selected cells. More particularly, this disclosure is directed to methods for delivering multiple materials and/or multiple doses of the same material to individual cells in a controlled variable manner.
Various methodologies have been proposed for delivering or introducing compounds into selected individual cells. For instance, microinjection techniques employ very small bore needles or micropipettes to manually inject material into the interior of the cell. The microinjection process involves penetration of the cell membrane using a microscope and a finely controlled holder. The holder can be used to place the material in a general region in the cytoplasm. Introduction of the micropipette perturbs the cell membrane and produces mechanical disturbances in the cell interior.
Electroporation is used to introduce agents into a fairly large population of cells in a non-discriminate manner using a transient electric field to produce holes or weaknesses in the cell membrane structure through which the agents may pass. Electro-injection is a combination of microinjection and electroporation in which a transient electric field is used to compromise or open the cell membrane followed by a pressure-driven microinjection procedure to introduce the desired material into the cytoplasm of a selected cell. Both methods involve perturbation of the cell membrane, which can change or alter cellular response to the agent or material under study or analysis. Devices and methodologies which can accurately deliver agents or compounds to targeted single cells either in isolation or in a cellular population in a manner which minimizes or eliminates mechanical or electrical disruption of the cell structure would be desirable.